Microfluidic systems are nowadays used in many technical fields. Microfluidic systems are used especially in the field of modern analytical methods. Modem analytical methods are characterized among others by the fact that only small amounts of sample are used for the analysis and hence the analytical systems prove to be economical with regard to active substances and are environmentally friendly. However, often only small amounts of sample are available for analysis thus requiring sample handling frequently in the range of a few microliters. Furthermore efforts are for example being made in the medical or diagnostic field to substantially minimize the amounts of sample. This should spare the patient from withdrawals of excessive amounts of body fluids such as for blood collection.
An essential prerequisite for handling small amounts of sample is among others that it must be possible to predetermine an exactly defined microstructure for sample processing. This is for example important for determining the concentration of an analyte in a sample since in this case a sample volume must often be defined on the basis of the microstructure.
However, when manufacturing microfluidic systems it turns out that, due to the manufacturing process, they frequently do not have exactly defined channel structures or cause so-called dead volumes depending on the manufacturing method e.g. branching sites of channels. In this case a portion of a fluid which is referred to as a dead volume is present in channel areas through which the flowing fluid does not pass due to channel branches or connections. Hence fluid located there is no longer available for the actual use once it is enclosed in this channel area. Determinations of concentration to mention only one example would thus be erroneous.
Microstructures which are particularly difficult to manufacture are in particular microfluidic systems with a high aspect ratio which are recently being used more and more frequently. A characteristic of microfluidic channels with a high aspect ratio is that they have a large depth which is aimed to be in a range of up to a few centimetres despite a small width in the range of only a few micrometers. An example of an application for channels with a high aspect ratio is for example filtration processes in which a filter material is located within a channel. When a sample is added to the channel, a filtrate forms in the lower region of the channel, for example due to the force of gravity, and can be collected there. In this case it is important that, on the one hand, the channel is characterized by an adequate depth in order that the filtration process can run to completion. On the other hand, the channel should only have a small width to ensure that the sample volume is minimized. An example of such filtration processes is the field of plasma isolation from blood. In this case the blood corpuscles are retained in the filter material in the upper region of the channel while the plasma can be isolated as a filtrate in the lower region of the channel. In principle numerous applications are conceivable and can in particular be in the field of sample preparation and in which particulate material such as sample components bound to particles is removed from the other sample components.
Another field of application for microfluidic channel systems with a high aspect ratio is the field of preparing liquid mixtures. In this case a wide variety of possible applications is also conceivable which require an effective mixing of small volumes of sample. Examples are the preparation of enzyme-substrate mixtures or in general the mixing of reagents and sample in which a small sample and/or reagent consumption plays an important role and hence the use of microstructures is particularly advantageous in this case. In general the use of microstructures with a high aspect ratio proves to be advantageous for example in the preparation of elution gradients, dilution series or concentration gradients to mention only a few examples as soon as only small fluid volumes are used.
Additional examples of application also arise from the field of analysing reaction products whose formation is initiated by mixing substances as well as analysing their kinetics. In order to measure kinetics it is important in this connection that the various substances which react with one another are immediately and completely mixed in order that one can assume that the start of the reaction is uniform for the entire sample.
It is of course also conceivable that the microfluidic structures result in a separation of complex samples or that such channel structures result in a continuous removal of a sample for analysis. This can for example enable a simultaneous determination of a plurality of analytes with a single sample application by simultaneously dividing the sample among several test fields by means of a selected fluid guidance.
In principle a variety of possible applications are conceivable especially for microstructures with a high aspect ratio. An integration of microfluidic channel systems is unavoidable especially in the field of modern analysis in which microstructural elements are often already used. Examples of this are microdialysis systems that are for example used to determine glucose in diabetics.
Hence many methods have been disclosed in the prior art for producing microfluidic systems with a high aspect ratio as well as methods for their use.
The patent U.S. Pat. No. 6,251,248 discloses an example of a microstructure which is formed as a result of a controlled swelling of a polymeric material. The system can be formed in a controlled manner by a controlled current flow by using an electrolytic solution and an ionomeric polymer. Furthermore microstructures are disclosed in the documents U.S. Pat. Nos. 6,068,684 and 6,051,866 which are manufactured by means of etching processes and irradiation. Various variants of etching and irradiation can be used which are for example known from structured exposures in the field of photosensitive coatings. The document WO 99/36941 uses the pattering of metal among others to produce microstructures.
All of the said methods of the prior art have the disadvantage that the manufacturing process makes particular requirements on the material for the microstructure depending on the selected process. Often it is difficult to exactly control the process for forming a channel and hence it is often not possible to ensure a uniform shaping of the channel structure. This is for example frequently the case in etching processes in which widening can occur in the upper region of the channel structure, whereas the lower channel end is tapered. Hence it is often the case that the manufacturing method imposes limitations on the production of a channel having a desired depth and thus on the selection of the aspect ratio which cannot be selected to be of any magnitude. Common processes in the prior art usually allow aspect ratios of <3. In addition the processes are often complicated so that high costs are incurred not only as a result of the materials necessary for the process but also due to the manufacturing processes themselves. Furthermore especially in the case of mixing liquids it turns out that, due to the manufacturing technology, the channel structures provided for this have, as already described, a low aspect ratio for a given cross-sectional area and hence for example the mixing of different samples is incomplete and slowed down. However, the selection of materials in accordance with the manufacturing process also limits the application of the respective microstructure. For example the channel walls of a microstructure that has been manufactured monolithically by means of stereolithography have very rough surfaces making it impossible to microscopically observe the microfluidic structure. Hence it would be impossible to use a microstructure manufactured in this manner in the analytical field in which for example it is intended to optically detect a fluid in the channel.